Thioether Analogues of Disulfide-Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis, Dimerisation and Consequences for Receptor Activation

ChemBioChem ◽  
2014 ◽  
Vol 16 (2) ◽  
pp. 293-301 ◽  
Author(s):  
Karolina Pulka-Ziach ◽  
Valeria Pavet ◽  
Neila Chekkat ◽  
Karine Estieu-Gionnet ◽  
Roman Rohac ◽  
...  
Keyword(s):  
Conformational Analysis ◽  
Cyclic Peptides ◽  
Death Receptor ◽  
Receptor Activation ◽  
Death Receptor 5

scholarly journals Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway

Oncogene ◽  
2002 ◽  
Vol 21 (17) ◽  
pp. 2623-2633 ◽  
Author(s):  
Qin He ◽  
Dong Ik Lee ◽  
Rong Rong ◽  
Myounghee Yu ◽  
Xiuquan Luo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Death Receptor ◽  
Death Receptor 5 ◽  
Endoplasmic Reticulum Calcium ◽  
Induced Apoptosis ◽  
Calcium Pool

scholarly journals Structural basis of LaDR5, a novel agonistic anti-death receptor 5 (DR5) monoclonal antibody, to inhibit DR5/TRAIL complex formation

2012 ◽  
Vol 13 (1) ◽  
pp. 40
Author(s):  
Chunxia Qiao ◽  
Meiyun Hu ◽  
Leiming Guo ◽  
Ming Lv ◽  
Zhou Lin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Complex Formation ◽  
Death Receptor ◽  
Structural Basis ◽  
Death Receptor 5

scholarly journals Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Death Receptor 5 Networks That Are Highly Organized

2012 ◽  
Vol 287 (25) ◽  
pp. 21265-21278 ◽  
Author(s):  
Christopher C. Valley ◽  
Andrew K. Lewis ◽  
Deepti J. Mudaliar ◽  
Jason D. Perlmutter ◽  
Anthony R. Braun ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Death Receptor ◽  
Death Receptor 5 ◽  
Necrosis Factor

scholarly journals p53-Mediated Oxidative Stress Enhances Indirubin-3′-Monoxime-induced Apoptosis in HCT116 Colon Cancer Cells by Upregulating Death Receptor 5 and TNF-related Apoptosis-inducing Ligand Expression

2019 ◽  
Author(s):  
Matharage Gayani Dilshara ◽  
Ilandarage Menu Neelaka Molagoda ◽  
Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽  
Yung Hyun Choi ◽  
Cheol Park ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Death Receptor ◽  
Chimeric Antibody ◽  
Ros Production ◽  
Death Receptor 5 ◽  
Homologous Protein ◽  
Anti Cancer ◽  
Ligand Expression ◽  
Induced Apoptosis ◽  
Factor C

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53-/- cells are insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis is promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulting in endoplasmic reticulum (ER) stress-mediated DR5 expression, which is upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with TRAIL synergistically enhanced I3M-induced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53-/- cells were resistant to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells.

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